RETRA: evaluating the transfusion rate with darbepoetin alfa 500 µg every 3 weeks in anaemic cancer patients receiving chemotherapy.

BACKGROUND: Anaemia is a highly prevalent condition in cancer patients impacting on morbidity, mortality and quality of life. Darbepoetin alfa (DA) 500 µg administered once every 3 weeks (Q3W) has been shown to be effective in patients with chemotherapy-induced anaemia. OBJECTIVE: This non-interventional study investigated the efficacy and usage patterns of DA 500 µg Q3W in routine clinical practice. RESEARCH DESIGN AND METHODS: Prospective data on adult anaemic cancer patients receiving DA 500 µg Q3W during chemotherapy was collected. Efficacy of DA treatment was measured as the red blood cell transfusion (RBCT) incidence, the change in Hb over time, hospitalisations for anaemia, and the change in Eastern Cooperative Oncology Group (ECOG) performance status between baseline and study end. Usage patterns were evaluated in Hb categories at baseline and week 16, DA dosage information, and adherence to the guidelines issued by the European Organisation for Research and Treatment of Cancer (EORTC). RESULTS: A total of 309 patients were included. The median study duration was 16 weeks and the overall transfusion rate was 19%. Significantly fewer patients required transfusions when DA was initiated at Hb 9.0-10.0 g/dL (19%), as compared to later at a Hb < 9.0 g/dL (50%, p = 0.0002). Transfusion-independent patients had fewer anaemia-related hospitalisations and better ECOG scores at the end of the study. A total of 83% of patients reached a Hb ≥ 11.0 g/dL during weeks 1-16. Physicians' adherence to Hb thresholds for DA initiation as recommended by the EORTC was observed in 83% of patients. CONCLUSIONS: In accordance with the recommended treatment objective for DA to minimise RBCTs, 81% of study patients remained free of RBCTs during DA 500 µg Q3W treatment and at an even higher rate if DA treatment was initiated before Hb fell below 9.0 g/dL.

Monitoring of cardiac function by serum cardiac troponin T levels, ventricular repolarisation indices, and echocardiography after conditioning with fractionated total body irradiation and high-dose cyclophosphamide.

OBJECTIVES: Highly differing rates of cardiac complications associated with high-dose cyclophosphamide (CY) have been reported, and only one clinical study has been performed on the cardiotoxic effects of CY monotherapy following total body irradiation (TBI). PATIENTS AND METHODS: We prospectively evaluated the potential cardiotoxic effects of conditioning with fractionated total body irradiation and high-dose cyclophosphamide (TBI/CY) by serial measurement of serum cardiac troponin T (cTnT), assessment of systolic and diastolic echocardiographic parameters and analysis of ventricular repolarisation indices (QT-dispersion and corrected QT-dispersion) in 30 adult patients with haematological malignancies undergoing haematopoietic stem cell transplantation. RESULTS: There was no evidence of pretreatment cardiac dysfunction in any patient. Although cTnT was determined serially for a median of 14 d after completion of conditioning, no elevated levels were observed. Echocardiographic parameters did not show any significant change at a median follow-up of 5 months except for one patient with evidence of impaired diastolic filling. No significant differences for mean values before and after high-dose CY were noted for ventricular repolarisation indices. Two patients had a significant increase in corrected QT-dispersion after CY without any other signs of cardiotoxicity. Congestive heart failure or arrhythmias were not observed. CONCLUSIONS: These data suggest that TBI/CY is safe with respect to cardiotoxicity in patients without pre-existing cardiac dysfunction. Hitherto unknown synergistic cardiotoxic effects of CY with other cytostatic drugs may constitute the major pathogenic factor of myocardial dysfunction after high-dose chemotherapy.

Amifostine in combination with erythropoietin and G-CSF promotes multilineage hematopoiesis in patients with myelodysplastic syndrome.

Ineffective hematopoiesis leading to profound cytopenias represents a major clinical problem in the management of patients with myelodysplastic syndrome (MDS). The aminothiol amifostine has shown to promote multilineage hematopoiesis both in vivo and in vitro in patients with MDS. We have treated 10 patients with 250 mg/m2 amifostine thrice weekly in combination with erythropoietin for 4 consecutive weeks followed by 2 weeks observation. Responding patients received the same 6 week schedule, while nonresponder received G-CSF in addition to erythropoietin and amifostine during the second treatment course. All patients experienced single or multilineage hematologic improvement, but only 2 reached transfusion independency. Moreover, response was durable only in a minority of patients and thus additional studies are warranted to further define the potential interaction of amifostine and growth factors.

No evidence for microsatellite instability or consistent loss of heterozygosity at selected loci in chronic myeloid leukaemia blast crisis.

The aim of the present study was to investigate loss of heterozygosity (LOH) or microsatellite instability in chronic myeloid leukaemia (CML) blast crisis at genomic locations which are known or postulated to harbour tumour suppressor genes. We studied 48 patients in blast crisis of myeloid (n = 31), lymphoid (n = 15), megakaryocytic (n = 1), or mixed lineage (n = 1) phenotype by comparing constitutional DNA extracted from buccal epithelial cells or chronic phase leucocytes with DNA obtained from blast crisis leucocytes. Twelve variable number tandem repeat loci from six different chromosomes were amplified by polymerase chain reaction using labelled primers, and fractionated on polyacrylamide gels. After autoradiography, length as well as intensity of the amplified products were compared between constitutional and blast crisis samples. LOH was scored as complete, partial or none in informative patients. Complete LOH was found in one patient at 8p22 and another at 13q14; partial LOH was detected in three patients at 11p13 and/or 11p15. No LOH was found at 6q27, 8p21, 18q21, 22q11-12 and 22q13 in any patient. Furthermore, no consistent difference in allelic length was observed in 517 paired amplifications indicating no microsatellite instability. We conclude that the Rb gene at 13q14, the Wilms tumour gene at 11p13, the DCC gene at 18q21, the neurofibromatosis 2 gene at 22q11-13 and uncloned tumour suppressor genes at 6q27, 8p21-22 and 11p15, as well as genes responsible for microsatellite instability, are unlikely to be involved in the progression of CML to blast crisis in the majority of patients.